Senile muscle atrophy represents one of the major problems associated with aging and is characterized by loss of strength and muscle mass. These changes restrict the mobility and independence of a growing segment of our society. This project will probe the cellular and molecular changes that occur during muscle aging. In particular, the function of skeletal muscle satellite cells will be evaluated. Satellite cells are the myogenic precursor cells that persist in muscle throughout life and function by adding new nuclei to existing muscle fibers during muscle hypertrophy and by regenerating new fibers following injury. Their ability to proliferate and differentiate in response to three important regulatory protein growth factors, or hormones, is being studied. These hormones are the two insulin-like growth factors (somatomedins) and fibroblast growth factor. In vitro techniques have been devised for monitoring the effects of growth factors on the proliferation and differentiation of cultured satellite cells, and these techniques will be employed to study the normal control of satellite cell activity. In addition, age-related changes in the ability of satellite cells to respond to these growth factors and changes in their growth factor receptor characteristics during aging will be examined. This research program is designed to provide fundamental insights into the cellular and molecular mechanisms of muscle aging with the ultimate goal of contributing toward the alleviation of problems associated with senile muscle atrophy.